2,6-dichlorobenzylidenehydrazides

ABSTRACT

NOVEL DERIVATIVES OF 2,6-DICHLOROBENZYLIDENEHYDRAZDES HAVE BEEN PREPARED WHICH HAVE USEFUL PHARMACOLOGICAL ACTIVITY.

United States Patent 3,836,580 2,6-DICHLOROBENZYLIDENEHYDRAZIDES WilliamF. Bruce, Havel-town, Pa., assignor to American Home ProductsCorporation, New York, N.Y.

No Drawing. Original application July 1, 1971, Ser. No. 159,056, nowPatent No. 3,746,703. Divided and this application Jan. 26, 1973, Ser.No. 326,938

Int. Cl. C07c 109/10 US. Cl. 260558 H Claims ABSTRACT OF THE DISCLOSURENovel derivativesof 2,6-dichlorobenzylidenehydrazides have been preparedwhich have useful pharmacological activity.

This is a division of application Ser. No. 159,056, filed July 1, 1971,now US. Pat. 3,746,703.

DESCRIPTION OF THE INVENTION This invention is concerned with novelpharmacological compounds of Formula I:

- 1i N HgC-N l m [0H3 o N no C I'IQ H R N R2 and wherein R R and R areindependently selected from the group consisting of hydrogen, halogen,hydroxy (lower)alkoxy, amino and (lower)alkyl and n is an integer from 1to 6.

The compounds of the invention are prepared by the admixture of2,6-dichlorobenzaldehyde with the appropriate substitutedlhydrazidederivative in the presence of an organic solvent.

' The compounds of Formula I of this invention have been found to exerta depressant action on the central nervous system when tested understandard and accepted pharmacological procedures, in animals, such asmice and rats. They are, therefore, deemed to possess utility inexperimental and comparative pharmacology and are of value to treatconditions in animals, such as valuable domestic animals, and inlaboratory animals, such as mice, rats and the like, responsive totreatment with central nervous system depressant agents. Specificallythe compounds may be employed to induce a calming effect in mammals.

"ice

In the pharmacological evaluation of the biological activity of thecompounds of this invention, the in vivo effects were tested as follows:The compound was administered orally to three mice (14 to 24 grams) ateach of the following doses: 400, 127, 40 and 12.7 milligrams perkilogram of host body weight (m.p.k.). The animals were watched for aminimum of two hours during which time signs of general stimulation(i.e. increased spontaneous motor activity, hyperactivity on tactilestimulation, twitching), general depression (i.e., decreased spontaneousmotor activity, decreased respiration), autonomic activity (i.e.,miosis, mydriasis, diarrhea) were noted.

The compounds of this invention induce central nervous system depressanteffects at a dose of about 40 to about 400 m.p.k.

In addition to the above-described depressant activity many of thecompounds possess useful hypotensive activity in mammals such as rats,at a dosage level of l0100 milligrams per kg. of body weight R0. Amongthose compounds which possess this activity are the following:

2,6-dichlorobenzylidene isonicotinic acid hydrazide;2,6dichlorobenzylidene nicotinic acid hydrazide; 2,6-dichlorobenzylidenebutyric acid hydrazide; 2,6-dichlorobenzylidene Z-methyllactic acidhydrazide; 2,6-dichlorobenzylidene 3-methylthiopropionic acid hydrazide;2,6-dichlorobenzylidene picolinic acid hydrazide;2,6-dichlorobenzylidene 3-pyridineacetic acid hydrazide;2,6-dichlorobenzylidene propionic acid hydrazide;2,6-dichlorobenzylidene diethylarninoacetic acid hydrazide;2,6-dichlorobenzylidene Z-pyridineacetic acid hydrazide;2,6-dichlorobenzylidene valeric acid hydrazide; 2,6-dichlorobenzylidenehexanoic acid hydrazide; 2,6-dichlorobenzylidene 6-aminonicotinic acidhydrazide; 2,6-dichlorobenzylidene 3-ethoxypropionic acid hydrazide;2,6-dichlorobenzylidene dimethylaminoacetic acid hydrazide;2,6-dichlorobenzylidene lactic acid hydrazide; 2,6-dichlorobenzylideneformic acid hydrazide; and 2,6-dichlorobenzylidene isobutyric acidhydrazide.

When the compounds of the invention are administered for the purpose ofinducing a therapeutic effect, they may be administered in combinationwith suitable diluents, solvents, excipients or carriers according tostandard pharmaceutical practice. Suitable methods of preparing suchcompositions are well-known to those skilled in the art. The carriersmay be selected from the group comprising lactose, sucrose, dextrose,starch, calcium carbonate or any other suitable ingredient. Otheringredients and materials for preparing oral or parenteral dosage formsmay be found in the text titled, Remingtons Practice of Pharmacy, 9thEd., Mack Pub. Co., Easton, Pa. (1948) or any other standard referencework.

Many of the starting materials are commercially available or may beprepared according to methods set forth in the literature or asdisclosed in the specific embodiments herein. 7

The following examples are given by way of. illustration and are notconstrued as limitations of this invention, many variations of which arepossible without departing from the scope and spirit thereof.

EXAMPLE I 2,6-Dichlorobenzylidene isonicotinic acid hydrazid A solutionof 9 g. of 2,6-dichlorobenzaldehyde in 40 ml. of ethanol, with 7 g. ofisonicotinic hydrazidein 15 ml. of acetic acid, heated two hours on asteam bath, gave on addition of 50 ml. of water 13 g. of white fibrouscrystals, m.p. 213-4".

' 3 FAnalysis-Calcd for c,,H,ci,N,o= C, 53.08; H, 3.08; Cl, 24.11; N,.14.29. Found: C, 52.85; H, 3.00; Cl, 24.14; N, 14.19.

EXAMPLE II 2,6-Dichlorobenzylidene salicylic acid hydrazide EXAMPLE III2,6-Dichlorobenzylidene nicotinic acid hydrazide A solution of 5 g. of2,6-dichlorobenzaldehyde in 30 ml. of ethanol, with 5 g. of nicotinichydrazide in 25 ml. of ethanol heated twenty minutes on a steam bathgave 9 g. of white needles, m.p. 209-10".

Analysis.'Calcd for C13H9C12N30': C, 53.08; H, 3.08; Cl, 24.11; N,14.24. Found: C, 53.04; H, 3.12; Cl, 23.94; N. 14.60.

EXAMPLE IV 2,6-Dichlrobenzylidene benzoic acid hydrazide A solution of3.5 g. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol, with 2.5 g. ofbenzoylhydrazine in 30 ml. of ethanol, was warmed on a steam bath togive 6 g. of flaky white crystals, m.p. 226-7 Analysis.Calcd. forC,,H,,C1,N,0; C, 57.36; H, 3.44; Cl, 24.19; N, 9.56. Found: C, 57.04; H,3.64; Cl, 24.34; N. 9.41.

EXAMPLE V '2,6-Dichlorobenzylidene p-anisic acid hydrazide A solution ofg. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol, with 4 g. ofp-anisoylhydrazine in 30 ml. of ethanol rapidly gave 8 g. of fibrouswhite crystals, m.p. 224-5".

Analysis.-Calcd for C H C1 N O C, 55.74; H, 3.74; CI, 21.94; N, 8.67.Found: C, 55.61; H, 3.88; Cl, 21.91; N, 8.40.

'EXAMPLE VI 2,6-Dichlorobenzylidene anthranilic acid hydrazide Asolution of 5 g. of .2,-6-dichlorobenzaldehyde in 30 ml. of ethanol,with 4.5 g. of anthraniloylhydrazine in 30 ml. of ethanol heated on asteam bath soon gave a voluminous White precipitate m.p. 237-8; 7 g.

Analysis.-Calcd. for C14H11C12N3OI C, 54.56; H, 3.60; CI, 23.01; N,13.64. Found: C, 54.43; H, 3.78; Cl, 23.02; N, 13.69.

EXAMPLE VII 2,6-Dichlorobenzylidene cinnamic acid hydrazide A solutionof 10 g. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol with 10 g. ofcinnamoylhydrazine in 30 ml. of ethanol, heated on a steam bath gave 3g. of yellow needles, m.p. 229-30".

Analysis. Calcd for C H Cl N O: C, 60.11; H, 3.79; CI, 22.18; N, 8.77.Found: C, 59.83; H, 3.85; Cl, 22.00; N,'8.90.

EXAMPLE VIII 2,6-Dichlorobenzylidene acetic acid hydrazide A solution of5 g. of 2,6-dichlorobenzaldehyde in 30 ml. ofethanol with 4.5 g. ofacetylhydrazine in 30 ml. of ethanol heated fifteen minutes on a steambath gave on cooling and seeding 5.5 g. of fine white needles, m.p.201-2".

. .1 .54 at, i Analysis.-Calcd for cmgcuN ofc, 46.76; 3.49; or, 30.68;N, 12.12.-Found: c, 46.52;-H, 3.51; 01 30.44; N, 12.39.

EXAMPLE IX 2,6-Dichlorobenzylidene butyric acid hydrazide N, 10.81.Found: 0, 50. 2; H, 4.38; N, 10.69;

EXAMPLE X 2,6-Dichlorobenzylidene Z-methyllactic acid hydrazide Amixture of 12 g. of methyl Z-hydroxyisobutyrate and 5 g. of hydrazinehydrate was heated at for two hours, then to for ten minutes gave oncooling 9 g. of white granular crystals of Z-methylacetylhydrazine whichwas recrystallized from ethanol, m.p. 98.9".

AnaL-Calcd for C H N O C, 40.66; H, 8.53; N, 23.71. Found: C, 40.78; H,8.44; N, 23.70.

A solution of 5 g. of this compound in 35 ml. of ethanol with 7 g. of2,6-dichlorobenzaldehyde in .30 ml. of ethanol heated twenty minutes ona steambath gave on long standing 8 g. of shiny white microcrystals,m.p. 205-6".

Anal.--Calcd for C H Cl N O C, 48.02; H, 4.40; Cl, 25.77; N, 10.18.Found: C, 48.13; H, 4.39; Cl, 25.62; N, 10.06.

EXAMPLE XI 2,6-Dichlorobenzylidene 3-methylthiopropio'nic acid hydrazideA mixture of 14 g. of methyl 3 methylthiopropionate and 6 ml. ofhydrazine hydrate with 10ml. of toluene heated gradually to 140 gavewhen cooled a solid (10 g.) which was crystallized from isopropanol togive 8" g. of white crystals, m.p. 158-9 after drying. i

A solution of 5 g. of this compound in25 ml. of ethanol with 6.5 g. of2,6-dichlorobenzaldehyde heated briefly on a steam bath gave 5 g. offluffy white" crystals, m.p. 148-9".

Anal.Calcd for c H cl N osz'C, 45.37; H, 4.16; Cl, 24.35; N, 9.62; S,11.01. Found: C, 45.20; H, 4.31; Cl, 24.14; N, 9.26; S, 10.94.

EXAMPLE XII 2,6-Dichlorobenzylidene picolinic acid hydrazide A solutionof 6 g. of picolinoylhydrazine in 25f ml. of ethanol with 8.5 g. of2,6-dichlorobenzal'dehyde in 25 ml. of ethanol, heated for ten minuteson a steam bath gave 11 g. of white fibrous crystals, m.p. 20910.

AnaL-Calcd for C H Cl N O: C, 53.08; H, 3.08; CI, 24.11; N, 14.26.Found: C, 52.86; H, 3.16; C], 24.21; N, 14.15.

EXAMPLE XIII obenzylidene 3,4,5-trimethoxybenzoie 1 4 acid hydrazide 40ml. of ethanol, heated fifteen minutes on a steam bath, gave 6 g. offine white crystals, m.p. 199200.

Anal.-Calcd for C H Cl N O: C, 54.56; H, 3.60; Cl, 23.01; N, 13.64.Found: C, 54.47; H, 3.66; CI, 23.31; N, 13.54.

EXAMPLE XV 2,6-Dichlorobenzylidene propionic acid hydrazide A solutionof 5 g. of propionylhydrazine in 25 ml. of ethanol with 6 g. of2,6-dichlorobenzaldehyde in 25 ml. of ethanol heated twenty minutes on asteam bath gave 5 g. of'white fibrous crystals, with a yellowish cast inthe-shadows, 171-2 Anal.Calcd for C H Cl N O: C, 49.00; H, 4.11; N,11.43. FoundrC, 48.88; H, 4.03; N, 11.2.

EXAMPLE XVI 2,6-Dichlorobenzylidene diethylaminoacetic acid hydrazide Asolution of 6.5 g. of 2,6-dichlorobenzaldehyde With 5 g. ofdiethylaminoacetylhydrazine in 50 ml. of ethanol, heated fifteen minuteson a steam bath gave after standing in an evaporating dish 6 g. of whiteneedles, m.p. 945. JAnaL-Calcd for C H Cl N O: C, 51.67; H, 5.67; Cl,23.46; N, 13.91. Found: C, 51.56; H, 5.42; Cl, 23.61; N, 13.76.

" EXAMPLE XvII 2,6-Dichlorobenzylidene p-hydroxybenzoic acid hydrazideEXAMPLE XVIII 2,6-Dichlorobenzylidehe p-aminobenzoic acid hydrazide Asolution of 6 g. of p-aminobenzoic acid hydrazide in '50 ml. of ethanolwith 7 g. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol heated tenminutes on a steam bath gave 8 g. of tiny yellowish plates, m.p. 2489.Anal.-Calcd C14H11C12N301 C, H, Cl, 23.01; N, 13.64. Found: C, 54.32; H,3.76; Cl, 22.96; N, 13.44.

' EXAMPLE XIX 2,6-Dichlorobenzylidene, mandelic acid hydrazide i Asolution of 5 g. of mandelic acid hydrazide in 20 ml. of ethanol, with6.5 g. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol heated half anhour on a steam bath gave 8 g. of white powdery crystals, m.p. 2067.

AnaL-Calcd for C H C1 N O C, 55.74; H, 3.74; N, 8167; Foundi C, 55.42;H, 3.87; N, 8.84.

EXAMPLE XX 2,6-'Dichloroben zylidene 2-pyridineacetic acid hydrazide 30ml. of ethanol, with 5 g. of 2,6-dichlorobenzaldehyde in 30 ml.. ofethanol, heated ten minutes on a steam bath, gave'6.5 g. of yellowneedles, m.p. 215*6.

. A'naL-Calcd for ,C H Cl N O: C, 54.56; H, 3.60; C1, 2301; N,13.645Foundz C, 54.57; H, 3.74; Cl, 23.00; N, 13.91.

' solution of 4 g. of 2-pyridineacetic acid hydrazide in I 6 EXAMPLE XXI2,6-Dichlorobenzylidene 1,2,3,6-tetrahydro-1,3-dimethy1-2,6-dioXopurine-7-acetic acid hydrazide A solution of 4 g. of7-theophylline acetic acid hydrazide in 20 ml. of ethanol with 15 ml. of6 N hydrochloric acid and 30 ml. of water, with 5 g. of 2,6-dichlorobenzaldehyde in 25 ml. of ethanol, heated one minute on a steambath, give 5 g. of white precipitate with yellowish sheen, m.p. 2956.

AnaL-Calcd for C H Cl N O C, 46.96; H, 3.45; N, 20.54. Found: C, 46.68;H, 3.52; N, 20.32.

EXAMPLE XXII 2,6-Dichlorobenzylidene 5-hydroxy-2-methylindole-3-carboxylic acid hydrazide A solution of 4 g. ofS-hydroXy-2-methylindole-3-carboxylic acid hydrazide in 20 ml. ofethanol and 15 ml. of dimethylformamide, with 5 g. of2,6-dichlorobenzaldehyde in 30 ml. of ethanol, combined hot, gave 4.5 g.of tan powder, m.p. 316-7 AnaL-Calcd for C17H13C12N302i C, H, N, 11.63.Found: C, 56.66; H, 3.98; N, 11.38.

EXAMPLE XXIII 2,6-Dichlorobenzylidene valeric acid hydrazide A solutionof 2 g. of valeric acid hydrazide in 25 ml. of ethanol, with 4 g. of2,6-dichlorobenzaldehyde in 20 ml. of ethanol, heated 20 minutes on asteam bath, gave on seeding 5 g. of yellow-white needles, m.p. -6.

Anal.-Calcd for C H Cl N O: C, 52.76; H, 5.17; Cl, 25.96; N, 10.26.Found: C, 52.64; H, 4.98; CI, 26.03; N, 10.12.

EXAMPLE XXIV 2,6-Dichlorobenzylidene indole-3-acetic acid hydrazide Asolution of 4 g. of indole-3-acetic acid hydrazide in 20 ml. of ethanol,with 4 g. of 2,6-dichlorobenzaldehyde in 25 ml. of ethanol, heated tenminutes on a steam bath, gave 8 g. of white powder, m.p. 214-5Anal.Calcd for C H C1 N O: C, 58.97; H, 3.78; Cl, 20.48; N, 12.14.Found: C, 58.93; H, 4.06; Cl, 20.20; N, 12.13.

EXAMPLE XXV 2,6-Dichlorobenzy1idene heptanoic acid hydrazide A solutionof 2 g. of heptanoic acid hydrazide, m.p. 812, in 20 m1. of ethanol,with 4 g. of 2,6-dichlorobenzaldehyde in 20 ml. of ethanol gave afterone hour on a steam bath and concentration in a crystallizing dish 3 g.of yellowish rosettes, m.p. 134-5".

Anal.Calcd for C14H13C12N201 C, H, Cl, 23.24; N, 9.30. Found: C, 55.61;H, 5.96; CI, 23.77; N, 9.20.

EXAMPLE XXVI 2,6-Dichlorobenzylidene 2-thiophenecarboxylic acidhydrazide A solution of 5 g. of 2-thiophenecarboxylic acid hydrazide in30 ml. of ethanol, with 6 g. of 2,6-dichlorobenzaldehyde in 30 ml. ofethanol, heated half an hour on a steam bath gave on cooling 5 g. ofwhite granular crystals, m.p. 202-3".

Anal.Calcd for C H Cl N OS: C, 48.17; H, 2.70; Cl,'23.70; N, 9.36; S,10.72. Found: C, 48.51; H, 2.97; C1, 23.48; N, 9.37; S, 10.43.

EXAMPLE XXVII 2,6-Dichlorobenzylidene hexanoic acid hydrazide A solutionof 5 g. of heXanoic acid hydrazide in 50 ml. of ethanol with 7 g. of2,6-dichlorobenzaldehyde in 30 ml. of warm ethanol, heated ten minuteson a steam bath, gave 11 g. of yellowish white powder, m.p. 1612.

7 AnaL-Calcd for c13H1 c12N2o: C, H, Cl, 24.69; N, 9.67. Found: C,54.12; H, 5.45; Cl, 24.92; N, 9.65.

EXAMPLE XVHI 2,6-Dichlorobenzylidene G-aminonicotinic acid hydrazide Asolution of 6 g. of 6-aminonicotinic acid hydrazide in 30 ml. of ethanolwith 4 g. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol heated tenminutes on a steam bath gave 3 g. of white powder, m.p. 210-11". Onrecrystallization from ethanol, the m.p. was raised to 219-20.

AnaL-Calcd for C H CI N O: C, 50.98; H, 4.67; Cl, 27.36; N, 10.81.Found: C, 50.90; H, 4.65; Cl, 27.59; N, 10.83.

EXAMPLE XXIX 2,6-Dichlorobenzylidene o-fluorobenzoic acid hydrazide Asolution of 3.5 g. of o-fluorobenzoic acid hydrazide in 30 ml. ofethanol, with 3.5 g. of 2,6-dichlorobenzaldehyde in 20 ml. of ethanol,heated ten minutes on a steam bath, gave g. of fiuffy White crystals,m.p. 2245.

EXAMPLE XXX 2,6-Dichlorobenzylidene isonipecotic acid hydrazide Asolution of 4 g. of isonipecotic acid hydrazide in 30 m1. of ethanol,with 5 g. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol, heated tenminutes on the steam bath, gave 5.5 g. of yellowish white powder, m.p.245-6 d.

AnaL-Calcd. for C H Cl N O: C, 52.01; H, 5.04; Cl, 23.62; N, 13.83.Found: C, 52.13; H, 5.26; Cl, 23.98; N, 13.21.

EXAMPLE XXXI 2,6-Dichlorobenzylidene m-toluie acid hydrazide A solutionof 6 g. of m-toluic acid hydrazide in 30 ml. of ethanol with 7 g. of2,6-dichlorobenzaldehyde in 30 ml. of ethanol, heated ten minutes on asteam bath, gave 11 g. of white fibrous crystals, m.p. 2456.

EXAMPLE XXXII 2,6-Dichlorobenzylidene 2-octynoic acid hydrazide Asolution of 3 g. of octynoic acid hydrazide, m.p. 201- 2, made byheating ethyl 2-octynoate with hydrazine (Anal.Calcd. for C H N O: C,62.30; H, 9.15; N, 18.17. Found: C, 61.87; H, 9.11; N, 18.56), washeated one hour on a steam bath with 4.5 g. of 2,6-dichlorobenzaldehydein 20 ml. of ethanol to give 6 g. of orangeyellow precipitate, m.p.194-5 Anal.Calcd. for C H Cl N O: C, 57.89; H, 5.18; Cl, 22.80; N, 9.00.Found: C, 57.57; H, 5.38; Cl, 22.80; N, 9.01.

EXAMPLE XXXIII 2,6-Dichlorobenzylidene phenylacetic acid hydrazide Asolution of 5 g. of phenylacetic acid hydrazide in 20 ml. of ethanol,with 6 g. of 2,6-dichlorobenzaldehyde in 30 m1. of ethanol, heated onehour on a steam bath, gave 6 g. of white crystalline powder, m.p. 204-5.

Anal.Calcd. for C H Cl N O: C, 58.65; H, 3.94; Cl, 23.08; N, 9.12.Found: C, 58.69; H, 4.15; C1, 22.89; N, 9.20.

EXAMPLE XXXIV 2,6-Dichlorobenzylidene 3,4-dimethylbenzoic acid hydrazideA solution of 4 g. of 3,4-dimethylbenzoic acid hydrazide in 30 ml. ofethanol, m.p. 123-4", made by heating ethyl 3,4-dimethylbenzoate withhydrazine (Anal.- Calcd. for C H N O: N, 17.06; Found: N, 16.52) with 5g. of 2,6-dichlorobenzaldehyde in 25 ml. of ethanol, heated 30 min. on asteam bath, gave 6 g. of white fibrous product, m.p. 247-8.

8 Anal.-Calcd. for c,,H,,c1 N,o= c, 59.82; H, 4.59;, (:1, 22.08; N,8.72. Found: 0, 59.82; H, 4.45; c1, 21196;, N, 8.90. g I EXAMPLE XXXV2,6-Dichlorobenzylidene 3-ethoxypropionic acid hydrazide A solution of 5g. of crude 3-ethoxypropionic acid hydrazide, made by heating3-ethoxypropionic acid ethyl ester with hydrazine, in 30 ml. of ethanol,with. 6g. of 2,6-dichlorobenzaldehyde in 30 ml. of ethanol gave at, oncea yellow precipitate, m.p. 6,'the azine of.,the aldehyde, which wasfiltered OE, and the filtrate was heated two hours on a steam bath, gave2.5 g. of white:- needles, m.p. l33-4.

Anal.-Calcd. for C H Cl N- O C, 49.84;.H, 4.77; N, 9.69. Found: C,49.69; H, 4.51; N, 9.39.

EXAMPLE XXXVI 2,6-Dichlorobenzylidene dimethylaminoacetic acid hydrazide2,6-Dichlorobenzylidene lactic acid hydrazide A solution of 7 g. ofsyrupy lactic acid hydrazide, con: taining some hydrazine, in 40 ml.ofethanol with 1,0 g. of 2,6-dichlorobenzaldehyde in 40 ml. of ethanol,heated ten minutes on a steam bath, gave 2 g. of the az.ine,ln1.p..153-4", which was removed by filtration. 'The filtrate: in acrystallizing dish gave 7 g. of white flaky solid, m.p. 121-2.

AnaL-Calcd. for c H Cl N O C, 46.00; H, 3.86; Cl, 27.16, N, 10.73.Found: C, 45.89; H, 3.99; Cl, 27.39; N, 11.08.

EXAMPLEXXXVIII 2,6-Dichlorobenzylidene cyanoacetic acid hydrazide Asolution of 4 g. of cyanoacetic acid hydrazide in 40 ml. of ethanol with5 g. of 2,-6-d ichlorobenzaldehyde in 30 m1. of ethanol, heated tenminutes on a steam bath, gave 7 g. of bull powder, m.p. 219-20 d. A

AnaL-Calcd. for C H Cl N O: C, 46.90; H, 276; C1, 27.69; N, 16.41.Found: C, 46.82; H, 2.79; Cl, 27.49;- N, 16.32.

EXAMPLE 2,6-Dichlorobenzylidene formic acid hydrazide A solution of 3 g.of formic acid hydrazide 25 ml. of ethanol, with 6 g. of2,6:dichlorobenzald ehyde 25 ml. of ethanol, heated tenniin'utes ona'ste'ain bathgaye a fibrous White precipitate, 6"g.', n1.p. -6".

Anal.Calcd. for C H CI N O: C, 44:26; H,"2.79;. Cl,' 32.67; N, 12.91.Found: 0, 44.02; 11,234; 1,:32,152; N, 13.12.

EXAMPLE XL 2,6-Dichlorobenzylidene isobutyric acid hydrazide A solutionof 4 g. of isobutyric acid hydrazide 20 ml. of ethanol, with 5 got2,6-dichlorohenzaldehydein 25 ml. of ethanol, heated ten minutes onasteambatli, gave 3.5 g. of yellowish-white flufi'y 'needles, m.p.203-48; -Amzl.-Calcd. fOrC H Cl- N O: c, 50.98;" 11,; 4.67; 01, 27.36;N, 10.81. Found: 0,150.90; 4.65; o1, 27.59; N, 10.83.

9 EXAMPLE XLI 2,6-Dichlorobenzylidene carbohydrazide A solution of 4 g.of 2,6-dichlorobenzaldehyde in 50 ml. of ethanol was added slowly to 5g. of carbohydrazide in 40 ml. of water and 5 ml. of acetic acid on asteam bath. On cooling, 2.3 g. of fluffy white crystals separated m.p.310 d. Recrystallized from ethanol, this melted at 2167.

Anal.Calcd. for C H Cl N O: C, 38.88; H, 3.26; Cl, 28.70; N, 22.68.Found: C, 38.86; H, 3.23; Cl, 28.90; N, 22.17.

I claim:

1. A compound selected from the group consisting of2,6-dichlorobenzylidene cinnamic acid hydrazide; 2,6-dichlorobenzylidenem-toluic acid hydrazide; 2,6-dichlorobenzylidene phenylacetic acidhydrazide and 2,6-dichlorobenzylidene 3,4-dimethylbenzoic acidhydrazide.

2. A compound as defined in Claim 1 which is: 2,6- dichlorobenzylidenecinnamic acid hydrazide.

10 3. A compound as defined in Claim 1 which is: 2,6-dichlorobenzylidene m-toluic acid hydrazide.

4. A compound as defined in Claim 1 which is: 2,6- dichlorobenzylidenephenylacetic acid hydrazide.

5. A compound as defined in Claim 1 which is: 2,6- dichlorobenzylidene3,4-dimethylbenzoic acid hydrazide.

References Cited Chemical Abstracts Index, vol. 70, p. 438 (1971). Ofleet al.: Z. Naturfursch, vol. 7B, pp. 44662 (1952).

HARRY I. MOATZ, Primary Examiner U.S. Cl. X.R.

260256, 293.76, 295 H, 326.13 R, 332.2 C, 465 D, 554, 559 H, 562 H;424253, 263, 266, 267, 274, 275, 304, 323, 324

